This application proposes to establish a Molecular Libraries Screening Center (UP-MLSC) exploiting existing and new space and facilities at the University of Pittsburgh, with membership from the University of Pittsburgh, Carnegie Mellon University and Sandia National Laboratories. The overall objective of the UPMLSC will be to develop, implement, and optimize robust, optical methods for the detection, characterization, and refinement of small molecules with desired biological and pharmacological properties in cell-free, cell-based, and model organism-based assays assigned by the MLSCN Steering Group. The goals of the UPMLSC will be (a) to validate assays for use in high throughput screening, (b) to use these assays with secondary assays and informatics to identify active small molecules from chemical libraries, (c) to facilitate the use of these assays nationally, (d) to disseminate information about compound activity, and (e) to assist in the further optimization of the lead compounds. We intend to exploit and expand the documented existing interactive strengths of the Center members in assay implementation, high throughput and high content screening, combinatorial chemical synthesis, and informatics. We have carefully selected members for the UP-MLSC because of their expertise in the above-mentioned Core areas and in anticipation of potential assays that will be submitted to the Center. Moreover, we have recruited individuals who are expert in the design and development of novel fluorescent probes that may be useful in implementing new HTS assays, and individuals who have experience with assay development with Drosophila and zebrafish, which will be the models for organism-based assays in the UP-MLSC. [unreadable] [unreadable]